Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American men. A family history of prostate cancer is one of the strongest risk factors for the disease. Both epidemiological and segregation analyses confirm that hereditary components are involved in prostate cancer etiology, with inheritance of rare, autosomal dominant alleles thought to explain incidence in some families. We hypothesize that hereditary prostate cancer genes will be localized through analyses of high-risk families with three or more affected first degree relatives, affected men in three generations, or siblings diagnosed at younger ages (<65 years). Towards this end, the Prostate Cancer Genetic Research Study (PROGRESS) has collected baseline data on 152 high-risk families. Using this resource, specific aims to be accomplished as part of this grant are: 1) To extend pedigrees and verify family history of cancer data for families segregating prostate cancer and other cancers, families with five or more living affected men, and non-Caucasian families, 2) To initiate recruitment of new high-risk minority families, particularly African American families, 3) To extend pedigrees and confirm linkage analyses using markers in the region of 1p36, which appears to be the locus for an hereditary prostate cancer gene (CAPB) in families with brain cancer, and, 4) To complete linkage analyses on the 152 families using six markers in the region of 1q24-25, which is the locus for the first hereditary prostate gene (HPC1) to be reported. Epidemiological and clinical data such as age at diagnosis, family cancer history, and tumor stage and grade will be used to stratify families into homogeneous subsets, maximizing power to identify linkage in this complex disease. Finding such linkages and associated genes may provide powerful insights into the underlying genetic defects involved in the development of prostate cancer, including both the hereditary and more common sporadic forms of the disease.